In this study, we investigated the effects of 4-n-butylresorcinol on melanogenesis in a spontaneously immortalized mouse melanocyte cell line, Mel-Ab. Our results show that 4-n-butylresorcinol significantly inhibits melanin synthesis in a concentration-dependent manner. In addition, it was also found to inhibit the activity of tyrosinase, the rate-limiting melanogenic enzyme. Several reports have indicated that the activation of extracellular signal-regulated kinase (ERK) or of Akt reduces melanin synthesis via microphthalmia-associated transcription factor (MITF) down-regulation. Accordingly, we examined the effects of 4-n-butylresorcinol on the ERK and Akt signaling pathways. 4-n-Butylresorcinol did not induce ERK, Akt activation, or MITF degradation, and had no effect on cAMP response element binding protein (CREB) phosphorylation, which stimulates MITF expression. In contrast, 4-n-butylresorcinol strongly reduced tyrosinase activity in a cell-free system. Moreover, 4-n-butylresorcinol showed an additive effect in combination with hinokitiol, which reduces MITF expression. These results show that the hypopigmentary effect of 4-n-butylresorcinol results from its direct inhibition of tyrosinase.